scholarly journals Measuring maladaptive avoidance: from animal models to clinical anxiety

Author(s):  
Tali M. Ball ◽  
Lisa A. Gunaydin

AbstractAvoiding stimuli that predict danger is required for survival. However, avoidance can become maladaptive in individuals who overestimate threat and thus avoid safe situations as well as dangerous ones. Excessive avoidance is a core feature of anxiety disorders, post-traumatic stress disorder (PTSD), and obsessive-compulsive disorder (OCD). This avoidance prevents patients from confronting maladaptive threat beliefs, thereby maintaining disordered anxiety. Avoidance is associated with high levels of psychosocial impairment yet is poorly understood at a mechanistic level. Many objective laboratory assessments of avoidance measure adaptive avoidance, in which an individual learns to successfully avoid a truly noxious stimulus. However, anxiety disorders are characterized by maladaptive avoidance, for which there are fewer objective laboratory measures. We posit that maladaptive avoidance behavior depends on a combination of three altered neurobehavioral processes: (1) threat appraisal, (2) habitual avoidance, and (3) trait avoidance tendency. This heterogeneity in underlying processes presents challenges to the objective measurement of maladaptive avoidance behavior. Here we first review existing paradigms for measuring avoidance behavior and its underlying neural mechanisms in both human and animal models, and identify how existing paradigms relate to these neurobehavioral processes. We then propose a new framework to improve the translational understanding of maladaptive avoidance behavior by adapting paradigms to better differentiate underlying processes and mechanisms and applying these paradigms in clinical populations across diagnoses with the goal of developing novel interventions to engage specific identified neurobehavioral targets.

2021 ◽  
Author(s):  
Tali Ball ◽  
Lisa A. Gunaydin

Avoiding stimuli that predict danger is required for survival. However, avoidance can become maladaptive in individuals who overestimate threat and thus avoid safe situations as well as dangerous ones. Excessive avoidance is a core feature of anxiety disorders, post-traumatic stress disorder (PTSD), and obsessive-compulsive disorder (OCD). This avoidance prevents patients from confronting maladaptive threat beliefs, thereby maintaining disordered anxiety. Avoidance is associated with high levels of psychosocial impairment yet is poorly understood at a mechanistic level. Many objective, laboratory assessments of avoidance measure adaptive avoidance, in which an individual learns to successfully avoid a truly noxious stimulus. However, anxiety disorders are characterized by maladaptive avoidance, for which there are fewer objective laboratory measures. We posit that maladaptive avoidance behavior depends on a combination of three altered neurobehavioral processes: (1) threat appraisal, (2) trait avoidance tendency, and (3) habitual avoidance. This heterogeneity in underlying processes presents challenges to the objective measurement of maladaptive avoidance behavior. Here we first review existing paradigms for measuring avoidance behavior and its underlying neural mechanisms in both human and animal models, and identify how existing paradigms relate to these neurobehavioral processes. We then propose a new framework to improve the translational understanding of maladaptive avoidance behavior by adapting paradigms to better differentiate underlying processes and mechanisms and applying these paradigms in clinical populations across diagnoses with the goal of developing novel interventions to engage specific identified neurobehavioral targets.


Author(s):  
Benjamin Greenberg ◽  
Sarah H. Lisanby

A few studies of transcranial magnetic stimulation (TMS) as an anxiety disorder treatment have been reported. In treatment studies, the focal application of TMS in the treatment of anxiety disorders has been guided by the present understanding of the neurocircuitry underlying these disorders. This article reviews the current state of the literature on the uses of TMS in the study and treatment of anxiety disorders, and discusses the implications for understanding their patho-etiology. Investigation of the possible therapeutic effects of repetitive TMS in obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), or any anxiety disorder remains at a preliminary stage. There have been promising initial observations in OCD, which require systematic testing in controlled studies. As far as PTSD is concerned, the available data suggest that additional TMS work is required. The observations need to be replicated in controlled settings to determine whether this approach will have value in treating anxiety disorders.


2017 ◽  
Vol 31 (10) ◽  
pp. 1302-1305 ◽  
Author(s):  
Paul Glue ◽  
Natalie J Medlicott ◽  
Sarah Harland ◽  
Shona Neehoff ◽  
Bridie Anderson-Fahey ◽  
...  

The N-methyl-D-aspartate receptor antagonist ketamine has rapid onset activity in treatment-resistant depression, post-traumatic stress disorder and obsessive compulsive disorder. Due to similarities in brain network activity in depression and anxiety disorders, we hypothesized that ketamine might also be active in other refractory anxiety disorders. We evaluated the efficacy and safety of ketamine in 12 patients with refractory generalized anxiety disorder and/or social anxiety disorder who were not currently depressed, using an ascending single dose study design (0.25, 0.5, 1 mg/kg administered subcutaneously) at weekly intervals. Within 1 h of dosing, patients reported reduced anxiety, which persisted for up to seven days. A dose-response profile was noted for anxiolytic effects, dissociative side effects, and changes in blood pressure and heart rate, with minor changes at 0.25 mg/kg, and progressively greater and more durable changes at the higher doses. Ten of 12 patients were treatment responders at 0.5–1 mg/kg. Ketamine was safe and well tolerated in this population. Ketamine may be a potential therapeutic alternative for patients with refractory generalized anxiety disorder/social anxiety disorder. Along with its demonstrated effectiveness in patients with treatment-resistant depression, obsessive compulsive disorder and post-traumatic stress disorder, these data raise the intriguing possibility that ketamine may have broad efficacy in disorders characterized by negative emotional states, and that these disorders may share a common precipitating neurobiology.


2015 ◽  
Vol 17 (3) ◽  
pp. 245-246 ◽  

The DSM-5 process, and the publication of DSM-5 in 2013, have had a considerable impact on the classification of anxiety disorders. Major changes included the reorganization of the chapter structure, individual groupings of disorders within each chapter from a life span viewpoint, and the use of specifiers. The DSM-5 chapter on anxiety disorders does not include obsessive-compulsive disorder or post-traumatic stress disorder. The chapter itself now reflects a developmental approach. The text of each disorder has been enhanced with short sections on development and course, risk and prognostic factors, etc. It is expected that the reformulation of anxiety disorders in DSM-5 will lead to greater precision in a variety of ways, as illustrated in the papers in this issue of Dialogues in Clinical Neuroscience. In summary, these changes in the way we classify anxiety disorders reflect our best view on the clinical empirical data and should prove useful in the assessment of specific anxiety disorders.


2011 ◽  
Vol 13 (4) ◽  
pp. 453-461 ◽  

Over the last few years, neuroimaging techniques have contributed greatly to the identification of the structural and functional neuroanatomy of anxiety disorders. The amygdala seems to be a crucial structure for fear and anxiety, and has consistently been found to be activated in anxiety-provoking situations. Apart from the amygdala, the insula and anterior cinguiate cortex seem to be critical, and ail three have been referred to as the "fear network." In the present article, we review the main findings from three major lines of research. First, we examine human models of anxiety disorders, including fear conditioning studies and investigations of experimentally induced panic attacks. Then we turn to research in patients with anxiety disorders and take a dose look at post-traumatic stress disorder and obsessive-compulsive disorder. Finally, we review neuroimaging studies investigating neural correlates of successful treatment of anxiety, focusing on exposure-based therapy and several pharmacological treatment options, as well as combinations of both.


1997 ◽  
Vol 171 (4) ◽  
pp. 346-350 ◽  
Author(s):  
J. V. Lucey ◽  
Durval C. Costa ◽  
Gwen Adshead ◽  
Martin P. Deahl ◽  
Geraldo Busatto ◽  
...  

BackgroundWe compared regional cerebral blood flow (rCBF) in three groups of patients with DSM–III–R anxiety disorders.MethodFifteen patients with obsessive–compulsive disorder (OCD), 15 with panic disorder with agoraphobia (PA), and 16 with post-traumatic stress disorder (PTSD) and a similar group of healthy controls were assessed on brain-dedicated high-resolution SPET.ResultsMANOVA revealed significant rCBF differences between diagnostic groups (F=4.4; d.f.=3, 57; P=0.007) and between cerebral regions (F=6.4; d.f.=1, 57; P=0.01) in OCD and PTSD compared with PA and healthy controls, limited to bilateral superior frontal cortices and right caudate nuclei. Whole brain blood flow correlated positively with anxiety (r=0.24, n=46, P=0.05). Beck depression scores correlated significantly negatively with left caudate rCBF (r= –0.24, n=46, P=0.05) and right caudate rCBF (r= –0.31, n=46, P=0.02). PTSD syndrome severity correlated significantly negatively with the left caudate (r=-0.49, n=16. P=0.03) and with right caudate rCBF (r=-0.7, n=16, P=0.001)ConclusionsFunctional rCBF differences in anxiety disorders could relate to repetitive, intrusive, distressing mental activity, prominent in both OCD and PTSD.


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